A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer

Jillian R Gunther; Awalpreet S Chadha; Sushovan Guha; Gottumukkala S Raju; Dipen M Maru; Mark F Munsell; Yan Jiang; Peiying Yang; Edd Felix; Marilyn Clemons; Geena George Mathew; Pankaj K Singh; John M Skibber; Miguel A Rodriguez-Bigas; George J Chang; Cathy Eng; Marc E Delclos; Christopher H Crane; Prajnan Das; Sunil Krishnan

doi:10.21037/jgo-22-259

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer

J Gastrointest Oncol. 2022 Dec;13(6):2938-2950. doi: 10.21037/jgo-22-259.

Authors

Jillian R Gunther¹, Awalpreet S Chadha², Sushovan Guha³, Gottumukkala S Raju⁴, Dipen M Maru⁵, Mark F Munsell⁶, Yan Jiang⁷, Peiying Yang⁷, Edd Felix⁸, Marilyn Clemons¹, Geena George Mathew¹, Pankaj K Singh⁹, John M Skibber¹⁰, Miguel A Rodriguez-Bigas¹⁰, George J Chang¹⁰, Cathy Eng¹¹, Marc E Delclos¹, Christopher H Crane¹², Prajnan Das¹, Sunil Krishnan¹³

Affiliations

¹ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Internal Medicine, The University of Alabama, Birmingham, AL, USA.
³ Division of Gastroenterology, Department of Medicine, University of Texas Medical School at Houston, Houston, TX, USA.
⁴ Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA.
¹⁰ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹ Department of Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹² Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹³ Vivian L. Smith Department of Neurosurgery, UT Health Science Center, Houston, TX, USA.

Abstract

Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods: From 2008-2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate.

Results: Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24-18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84-5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8-258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1-4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced.

Conclusions: The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy.

Trial registration: ClinicalTrials.gov identifier: NCT00745134.

Keywords: Locally advanced rectal cancer (LARC); chemoradiation; curcumin.

Associated data

ClinicalTrials.gov/NCT00745134

Abstract

Associated data

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